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Activin receptor-like kinase 1 is associated with immune cell infiltration and regulates CLEC14A transcription in cancer

Bocci, Matteo LU ; Sjölund, Jonas LU ; Kurzejamska, Ewa LU ; Lindgren, David LU ; Marzouka, Nour Al Dain LU ; Bartoschek, Michael LU ; Höglund, Mattias LU and Pietras, Kristian LU (2018) In Angiogenesis
Abstract

Cancer cells sustain their metabolic needs through nutrients and oxygen supplied by the bloodstream. The requirement for tumor angiogenesis has been therapeutically exploited in the clinical setting mainly by means of inhibition of the vascular endothelial growth factor family of ligands and receptors. Despite promising results in preclinical models, the benefits for patients proved to be limited. Inadequate efficacy similarly halted the development of agents impinging on the activity of the activin receptor-like kinase (ALK)1, a member of the transforming growth factor-β superfamily. Notwithstanding its characterization as an endothelial cell marker, the full spectrum of biological processes associated with ALK1 is essentially... (More)

Cancer cells sustain their metabolic needs through nutrients and oxygen supplied by the bloodstream. The requirement for tumor angiogenesis has been therapeutically exploited in the clinical setting mainly by means of inhibition of the vascular endothelial growth factor family of ligands and receptors. Despite promising results in preclinical models, the benefits for patients proved to be limited. Inadequate efficacy similarly halted the development of agents impinging on the activity of the activin receptor-like kinase (ALK)1, a member of the transforming growth factor-β superfamily. Notwithstanding its characterization as an endothelial cell marker, the full spectrum of biological processes associated with ALK1 is essentially unexplored. Here, we present data revealing the genetic network associated with ACVRL1 (the gene encoding for ALK1) expression in human cancer tissues. Computational analysis unveiled a hitherto unknown role for ACVRL1 in relation to genes modulating the functionality of the immune cell compartment. Moreover, we generated a signature of 8 genes co-expressed with ACVRL1 across different tumor types and characterized the c-type lectin domain containing protein (CLEC)14A as a potential downstream target of ACVRL1. Considering the lack of reagents for ALK1 detection that has hampered the field to date, our work provides the opportunity to validate the 8-gene signature and CLEC14A as biomarkers for ALK1 activity. Ultimately, this may help revisit the clinical development of already existing ALK1-blocking compounds as precision medicines for cancer.

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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
ALK1, Angiogenesis, Cell signaling, Endothelial cell, Pathophysiology, Tumor biology
in
Angiogenesis
publisher
Springer Netherlands
external identifiers
  • scopus:85052089416
ISSN
0969-6970
DOI
10.1007/s10456-018-9642-5
language
English
LU publication?
yes
id
8784c466-8d1f-4375-9bab-f72a22d3d7e0
date added to LUP
2018-09-28 08:08:02
date last changed
2019-04-21 05:17:09
@article{8784c466-8d1f-4375-9bab-f72a22d3d7e0,
  abstract     = {<p>Cancer cells sustain their metabolic needs through nutrients and oxygen supplied by the bloodstream. The requirement for tumor angiogenesis has been therapeutically exploited in the clinical setting mainly by means of inhibition of the vascular endothelial growth factor family of ligands and receptors. Despite promising results in preclinical models, the benefits for patients proved to be limited. Inadequate efficacy similarly halted the development of agents impinging on the activity of the activin receptor-like kinase (ALK)1, a member of the transforming growth factor-β superfamily. Notwithstanding its characterization as an endothelial cell marker, the full spectrum of biological processes associated with ALK1 is essentially unexplored. Here, we present data revealing the genetic network associated with ACVRL1 (the gene encoding for ALK1) expression in human cancer tissues. Computational analysis unveiled a hitherto unknown role for ACVRL1 in relation to genes modulating the functionality of the immune cell compartment. Moreover, we generated a signature of 8 genes co-expressed with ACVRL1 across different tumor types and characterized the c-type lectin domain containing protein (CLEC)14A as a potential downstream target of ACVRL1. Considering the lack of reagents for ALK1 detection that has hampered the field to date, our work provides the opportunity to validate the 8-gene signature and CLEC14A as biomarkers for ALK1 activity. Ultimately, this may help revisit the clinical development of already existing ALK1-blocking compounds as precision medicines for cancer.</p>},
  author       = {Bocci, Matteo and Sjölund, Jonas and Kurzejamska, Ewa and Lindgren, David and Marzouka, Nour Al Dain and Bartoschek, Michael and Höglund, Mattias and Pietras, Kristian},
  issn         = {0969-6970},
  keyword      = {ALK1,Angiogenesis,Cell signaling,Endothelial cell,Pathophysiology,Tumor biology},
  language     = {eng},
  month        = {08},
  publisher    = {Springer Netherlands},
  series       = {Angiogenesis},
  title        = {Activin receptor-like kinase 1 is associated with immune cell infiltration and regulates CLEC14A transcription in cancer},
  url          = {http://dx.doi.org/10.1007/s10456-018-9642-5},
  year         = {2018},
}